POS0668 THE EFFICACY OF TOFACITINIB ON CLINICAL DYNAMIC AND CONCENTRATION OF CYTOKINES IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: N. Lapkina, A. Baranov, N. Levshin, N. Abaitova, A. Avdeeva, E. Leontieva, A. Artyuhov, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2022)

Background Pathogenesis of RA includes numerous interactions of genetic and acquired defects in normal immunoregulation, one is disbalance of pro- and anti-inflammatory cytokines production. Basic treatment conception in RA is «treat-to-target», including biological agents and Janus kinase (JAK) inhibitors. Tofacitinib is one of the first JAK-inhibitors in clinical practice, but data on its influence on cytokine profile during course of treatment are still limited. Objectives To study the dynamics of clinical signs, laboratory parameters of inflammatory activity and cytokines profile in RA patients treated with tofacitinib. Methods A total of 10 adults with valid diagnosis of RA (ACR/EULAR, 2010) and high disease activity (DAS28 5,88 [5,53; 5,94], CDAI 33.0 [29.0; 36.0], SDAI 33.72 [30.75; 36.85] score) were enrolled to the study. Mean age was 51,0 [48,0; 62,0] years, median disease duration 7.0 [3,0;20.0] years. All patients received TOFA 5 mg bid, methotrexate, non-steroidal anti-inflammatory drugs. There were 3 control points: before treatment, 3 and 6 months of tofacitinib treatment. Concentration of IL-1β, IL-4, IL-6, TNF-α, INF-γ, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, sCD40L were studied using multiplex technology (Bio-PlexTM 200 System, BIO-RAD, USA). Results Significant decrease in RA activity was marked after 3 and 6 months of treatment with tofacitinib - DAS28 of 4.55 [3.47; 5.16], 3.92 [3.80; 4.60]; CDAI 16.5 [11.0; 23.0], 18.0 [15.0; 19.0]; SDAI 16.6 [11.23; 23.06], 18.07 [15.06; 19.10]; ESR 19.0 [11.0; 26.0], 7.0 [4.0; 18.0]; CRB 0.56 [0.50; 1.99], 0.71 [0.51; 1.1], respectively. IL-6 levels decreased after 3 and 6 months of therapy (p&lt;0.05). The concentration of IFN-γ significantly decreased after 3 months (p&lt;0.05) but remained unchanged thereafter. Concentrations of IL-25 and IL-31 decreased after 3 months (p&lt;0.05), and by the 6th month of treatment there was an increase, but not reaching the initial values. The results of the study are shown in Table 1 Table 1. Levels of cytokines in RA patients receiving tofacitinib, pg/ml, Me [25;75 percentile]. Cytokine Initial After 3 months of tofacitinib treatment After 6 months of tofacitinib treatment IL-1β 0,07 [0,03;0,13] 0,05 [0,03;0,08] 0,08 [0,06;0,11] IL-4 4,28 [3,32;10,42] 3,96 [2,49;13,25] 7,03 [3,69;13,46] IL-6 3,43 [2,44;11,02] 2,28 [1,62;3,85]* 1,55 [1,33;2,07]* TNF-α 1,35 [0,68;2,41] 1,11 [0,68;1,76] 0,95 [0,49;1,57] IFN-γ 2,05 [1,48;3,19] 0,99 [0,49;2,05]* 0,99 [0,49;2,62]* IL-10 2,96 [1,20;2,56] 2,10 [1,50;3,04] 2,41 [1,80; 3,99] IL-17А 1,57 [0,42;2,17] 1,20 [0,71;1,72] 1,27 [0,85;1,27] IL-17F 2,49 [1,25;12,38] 1,56 [0,0;3,30] 2,49 [1,87;5,97] IL-21 4,74 [1,19;49,36] 2,07 [0,0;5,93] 4,75 [4,75;10,46] IL-22 2,76 [0,63;4,10] 1,18 [0,94;2,21] 2,21 [0,32;3,94] IL-23 13,54 [7,34;46,27] 10,26 [4,41;19,74] 13,90 [8,80;20,46] ИЛ-25 1,11 [0,32;2,18] 0,31 [0,0;1,25]* 0,42 [0,21;1,4]* IL-31 6,95 [3,85;17,72] 3,00 [1,50;3,85]* 5,09 [3,85;6,33]* IL-33 13,66 [8,72;38,48] 8,10 [3,90;22,37] 14,07 [9,96;26,09] sCD40L 72,77 [8,90;201,18] 15,31 [4,29;34,80] 40,17 [26,53;68,55] *p&lt;0,05 (comparing with initial concentration) Conclusion The data obtained indicate the efficacy of tofacitinib in patients with RA, including decreasing of disease activity and concentrations of clue pro-inflammatory cytokines. Further studies are needed to investigate pathogenic role of cytokine-mediated inflammation in RA and the efficacy of targeted oral medications on the course of the disease. Disclosure of Interests None declared